Medicaments for treating respiratory and nasal disorders are frequently administered in aerosol formulations through the mouth or nose. One widely used method for dispensing such an aerosol formulation involves making a suspension formulation of the medicament as a finely divided powder in a liquefied gas known as a propellant. Pressurised metered dose inhalers, or (pMDI's) are normally used to dispense such formulations to a patient. Surface active agents, or surfactants, are commonly included in order to aid dispersion of the medicament in the propellant and to prevent aggregation of the micronised medicament particles, and to improve lubrication of the valve.
Until recently, chlorofluorocarbon-containing propellants (CFC's) were accepted for use in all pharmaceutical aerosol formulations. Typical surfactant dispersing agents used in the CFC formulations were for example sorbitantrioleate, oleic acid, lecithines, and ethanol. Since CFC's have been implicated in the destruction of the ozone layer, a new generation of propellants has emerged to take their place.
Hydrofluoroalkane (HFA) propellants for example 1,1,1,2-tetrafluoroethane (P134a), 1,1,1,2,3,3,3-heptafluoropropane (P227) and 1,1-difluoroethane (P152a) are today considered to be the most promising new propellants. Not only are they environmentally acceptable, but they also have low toxicity and vapour pressures suitable for use in aerosols. However, the surfactants commonly used with the CFC formulations are not necessarily suitable for use with the new generation of propellants. Various alternative surfactants have been proposed.
For example, WO 92/00061 discloses polyethoxylated surfactant for use with hydrofluorocarbon propellants. WO 91/11173 discloses fluorinated surfactants. WO 91/14422 discloses perfluorinated carboxylic acid propellants for use with hydrofluorocarbon propellants. WO 92/00107 discloses the use of a 1,1,1,2-tetrafluoroethane-soluble surfactant with 1,1,1,2-tetrafluoroethane propellant.